title: Cytotoxic and antineoplastic activity of timosaponin A-III for human colon cancer cells.
abstract: The potential antitumor activity of timosaponin A-III (1), a steroidal saponin from the rhizomes of Anemarrhena asphodeloides, was investigated in human colorectal cancer HCT-15 cells both in cell culture and in an in vivo murine xenograft model. Compound 1 inhibited the proliferation of cancer cells with cell-cycle arrest and induction of apoptosis. Cell-cycle arrest in the G0/G1 and G2/M phase by 1 was correlated with the down-regulation of cyclin A, cyclin B1, cyclin-dependent kinase 2 (CDK2), CDK4, proliferating cell nuclear antigen, and c-Myc. The increase of the sub-G1 peak by 1 was also closely related to the induction of apoptosis, which was evidenced by the induction of DNA fragmentation, activation of caspases, induction of cleaved poly-(ADP ribose) polymerase, and suppression of Bcl-xL and Bcl-2 expression. In an in vivo xenograft model, treatment with 1 (2 or 5 mg/kg body weight, three times/week, ip administration) for four weeks significantly suppressed tumor growth in athymic nude mice bearing HCT-15 cells, without any overt toxicity. Cell-cycle arrest and induction of apoptosis might be plausible mechanisms of actions for the observed antineoplastic activity of 1.
authors.affiliation: College of Pharmacy, Center for Cell Signaling & Drug Discovery Research, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Kang
authors.forename: Hwa-Jin
authors.initials: HJ
authors.lastname: Chung
authors.forename: Joo-Won
authors.initials: JW
authors.lastname: Nam
authors.forename: Hyen Joo
authors.initials: HJ
authors.lastname: Park
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Seo
authors.forename: Yeong Shik
authors.initials: YS
authors.lastname: Kim
authors.forename: Dongho
authors.initials: D
authors.lastname: Lee
authors.forename: Sang Kook
authors.initials: SK
authors.lastname: Lee
mesh_terms: D031403:Anemarrhena / Q000737:chemistry*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D027343:Rhizome / Q000737:chemistry; D012503:Saponins / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D013256:Steroids / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D012503:Saponins; D013256:Steroids; C543146:timosaponin AIII; D011065:Poly(ADP-ribose) Polymerases; D051357:Cyclin-Dependent Kinase 2